Salutary Effects of Prostacyclin in Endotoxic Shock

Abstract

Endotoxin shock was induced in anesthetized cats with E. coli endotoxin (5 mg/kg, i.v.). This produced a severe decline in mean arterial blood pressure and a marked decrease in superior mesenteric artery flow (SMAF) within 1 h. The plasma activity of cathepsin D, a lysosomal protease, increased 6-fold by 2 h. At 5 h, myocardial depressant factor (MDF), a toxic peptide, accumulated in the plasma at very high activities. Infusion of prostacyclin (PGI₂) at rates of 0.75 nmol·kg^–1 • min^–1 dilated the splanchnic circulation and significantly increased SMAF. In addition, PGI₂ almost completely prevented the accumulation of cathepsin D and MDF in the circulating blood of cats given endotoxin. These findings suggest that PGI₂ exerts a variety of beneficial actions in endotoxin shock including vasodilation and stabilization of lysosomal membranes. In addition, PGI₂ is known to prevent platelet aggregation and suppress thromboxane formation, two additional effects that may be of positive survival value in endotoxin shock.